柔肝降酶方对四氯化碳诱导的大鼠急性肝损伤的作用研究

Effect of Rougan Jiangmei Fomula on Acute Liver Injury in Rats Induced by CCl_(4)

目的探讨柔肝降酶方对四氯化碳(CCl_(4))诱导的大鼠肝损伤的作用及机制。方法雄性SD大鼠40只随机分为对照组、模型组、柔肝降酶方组、水飞蓟宾组,每组10只。柔肝降酶方组以9.9 g/kg柔肝降酶方水煎液灌胃,水飞蓟宾组以54.6 mg/kg水飞蓟宾水溶液灌胃,对照组和模型组给予等剂量的生理盐水,连续给药7 d。给药结束2 h后,除对照组大鼠腹腔注射5 mL/kg橄榄油溶液外,其余各组大鼠腹腔注射等体积25%CCl_(4)橄榄油溶液制备急性肝损伤模型;1 d后使用谷丙转氨酶(ALT)、谷草转氨酶(AST)试剂盒检测大鼠血清ALT、AST;观察大鼠肝组织的形态学变化;Western blot检测炎性因子肿瘤坏死因子-α(TNF-α)、炎症因子白细胞介素-6(IL-6)蛋白表达水平,通路因子酪氨酸蛋白激酶1(JAK1)、磷酸化酪氨酸蛋白激酶1(p-JAK1)、信号传导及转录激活因子3(STAT3)、磷酸化信号传导及转录激活因子3(p-STAT3)蛋白表达水平。结果与对照组比较,模型组大鼠肝脏组织小叶结构破坏,肝细胞肿胀变形,大量脂肪空泡;血清ALT、AST水平显著升高(P<0.01);肝组织TNF-α、IL-6、p-JAK1、p-STAT3蛋白表达水平明显升高(P<0.05)。与模型组比较,柔肝降酶方组和水飞蓟宾组大鼠肝脏结构损伤程度减轻;血清ALT、AST水平显著降低(P<0.05);肝组织TNF-α、IL-6、p-JAK1、p-STAT3蛋白表达水平明显降低(P<0.05)。结论柔肝降酶方具有保护肝组织,减少炎症反应的作用,其机制可能与调节JAK1/STAT3信号通路有关。

Objective To investigate the effect of Rougan Jiangmei Fomula on liver injury in rats induced by CCl_(4).Methods 40 male SD rats were randomly divided into control group, model group, Rougan Jiangmei Fomula group and Silybin group, with 10 rats in each group.Rougan Jiangmei Fomula was infused at 9.9 g/kg rougan jiangmei fomula, silibin at 54.6 mg/kg silybin solution, the control group and model group were given equal dose of normal saline solution for 7 days.Two hours after the last administration, a model of acute liver injury was prepared by intraperitoneal injection of an equal volume of 25% CCl_(4) olive oil solution in each group, except for rats in the control group which were injected intraperitoneally with 5 mL/kg of olive oil solution.After 1 day, the serum ALT and AST levels of rats were measured using the glutathione transaminase(ALT) and glutathione aminotransferase(AST) kits.Morphological changes of rat liver tissues were observed using hematoxylin-eosin(HE) staining.The protein expression levels of inflammatory factor tumour necrosis factor-α(TNF-α),inflammatory factor interleukin-6(IL-6),pathway factor tyrosine protein kinase 1(JAK1),phosphorylated tyrosine protein kinase 1(p-JAK1),signal transducer and activator of transcription 3(STAT3),phosphorylated signal transducer and activator of transcription 3(p-STAT3) were measured by Western blot.Results Compared with the control group, the rats in the model group had disrupted liver tissue lobular structure, swollen and deformed hepatocytes, and a large number of fat vacuoles.Serum ALT and AST levels were significantly increased(P<0.01).The expression levels of TNF-α,IL-6,p-JAK1 and p-STAT3 proteins in liver tissues were significantly increased(P<0.05).Compared with the model group, the degree of liver structural damage was reduced in Rougan Jiangmei Fomula group and Silybin group.Serum ALT and AST levels were significantly reduced(P<0.05).The expression levels of TNF-α,IL-6,p-JAK1 and p-STAT3 proteins in liver tissues were significantly reduced(P<0.05).Conclusion Rougan Jiangmei Fomula can protect the liver tissue and reduce the inflammatory response and the mechanism may be related to the JAK1/STAT3 signaling pathway.